THE OXIDATIVE INACTIVATION OF CYTOCHROME-P450 IN MONOOXYGENASE REACTIONS

被引:78
作者
KARUZINA, II [1 ]
ARCHAKOV, AI [1 ]
机构
[1] RUSSIAN ACAD MED SCI, INST BIOL & MED CHEM, POGODINSKAYA STR 10, MOSCOW 119832, RUSSIA
关键词
CYTOCHROME-P450; SUICIDE INACTIVATION; HYDROGEN PEROXIDE; OXYGEN RADICALS; OXIDATIVE MODIFICATION; MONOOXYGENASE REACTIONS; CATALASE INHIBITORS; FREE RADICALS;
D O I
10.1016/0891-5849(94)90245-3
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Possible mechanisms of cytochrome P450 self-inactivation during catalytic turnover have been considered. Two ways of hemoprotein inactivation are so far known. The first, studied extensively by many authors, is the formation of active substrate intermediates, capable of modifying heme and apoenzyme. The second way, revealed quite recently and resulting from uncoupled cytochrome P450-catalyzed monooxygenase reactions, is yet to be clarified. Briefly, it involves formation of hydrogen peroxide in the hemoprotein active center, which interacts with the enzyme associated Fe2+, thereby generating hydroxyl radicals that bleach the heme and modify the apoenzyme. This mechanism operates with substrates and cytochrome P450 forms with partially coupled monooxygenase reactions, thus causing the formation of hydrogen peroxide as a byproduct.
引用
收藏
页码:73 / 97
页数:25
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